Heretofore, in an excision surgery of a cancer, in many cases, not only a lesion part but also a lymph node to which metastasis of the cancer is suspected has been excised. In recent years, a sentinel lymph node biopsy has been performed in order to minimize the excision of the lymph node.
The sentinel lymph node (SLN) is defined as a lymph node that first receives lymph flows from the respective internal organs. In the cancer surgery, such a sentinel lymph node theory is widely accepted that a radical lymph node dissection is unnecessary unless metastasis of the cancer to the sentinel lymph node is present. The sentinel lymph node biopsy makes it possible to reduce a wasteful surgical invasion, and contributes to establishment of order-made medical care in which a surgical method is finely selected in response to patient's symptoms.
In the event of performing the sentinel lymph node biopsy, it is important to enhance a detection sensitivity for a true sentinel lymph node during the surgery, and to enhance diagnosis accuracy as to whether or not the metastasis of the cancer is present in an inside of such an extirpated sentinel lymph node.
At present, materials clinically used as tracers which identify the sentinel lymph node during the surgery are coloring matter (Patent Blue, India ink and the like) and a radio isotope (RI) colloid (99nTc and the like); however, both of them also have many shortcomings. For example, in the case of the coloring matter, there are problems, which are: (1) in the case where dirt of anthracosis or the like is nonspecifically present in a lymph node in a living body, it becomes impossible to make evaluation as to whether or not the lymph node concerned is the sentinel lymph node; (2) an area from which the lymph node is to be dissected is contaminated, resulting in disturbance to the surgery; (3) the patient has allergy (anaphylactic reaction) to the coloring matter; and the like. Meanwhile, in the case of the RI colloid, there are such problems, which are: (1) a particle diameter of the colloid is several hundred nanometers to several ten micrometers, which is larger in comparison with those of the coloring matter (with several nanometers) and quantum dots (with several ten nanometers), and the colloid is poor in shifting to a lymphatic system, and accordingly, such a lymph flow cannot be observed in real time; (2) since resolution is low, there is an apprehension that the sentinel lymph node may escape detection in the case where the sentinel lymph node is located in the vicinity of a part into which the colloid is to be locally injected (shine-through phenomenon); (3) the RI colloid is regulated with regard to use thereof, and it is difficult to expand adaptable facilities thereof; and the like.
Moreover, in comparison with a cancer of a region having a relatively simple lymph flow, such as abreast cancer and a skin cancer, in a digestive system cancer in which the lymph flow is multi-directional and complicated, it is difficult to observe the lymph flow in real time, and accordingly, application of such a sentinel lymph node biopsy method is delayed.
For the above-described reasons, development of a new tracer excellent in detection sensitivity is expected, and there is proposed a method for detecting the sentinel lymph node, which uses fluorescent coloring matter (refer to Patent Document 1 and Patent Document 2). In particular, it is considered to be possible that quantum dots (Ws) can be such a tracer for the sentinel lymph node, which has an excellent detection sensitivity
It is the largest object of the sentinel lymph node biopsy to diagnose whether or not metastatic cancer cells are present in the sentinel lymph node during the surgery. At present, the diagnosis as to whether or not the cancer metastasis to the sentinel lymph node is present is performed by a microscope after an extirpated tissue is sliced, and is stained by hematoxylin-eosin staining or the like. However, since only a tiny part of the extirpated lymph node tissue just can be observed, there is a risk that minute metastasis may escape detection. For example, in the case of a lymph node with a diameter of approximately 5 mm, even if one to three cross sections thereof are inspected, these cross sections are no more than 0.01% of the whole thereof.
In order to enhance capability of diagnosing whether or not the cancer is present, there are attempted: (1) a multiple staining method in which several types of immunostaining are combined with one another; (2) a technique for detecting the cancer cells in the inside of the tissue by extracting RNA from the whole of the lymph node tissue and performing a reverse transcriptase-polymerase chain reaction (RT-PCR) therefor; and the like. However, in the multiple staining method, as in the usual staining method, there is an apprehension that the metastasis cells may escape detection at a stage of creating a tissue slide. Moreover, the RT-PCP method has such shortcomings that the inspection is cumbersome and requires a time though the detection capability for the cancer cells is high, and the RT-PCR method concerned is not suitable for rapid diagnosis during the surgery, that only information in which the whole of the tissue is averaged is obtained, that it becomes impossible to make a pathological sample since it is necessary to inspect the whole of the tissue in order to surely find the minute metastasis, and the like.
Hence, in the pathological diagnosis in the sentinel lymph node biopsy, it is considered to be necessary to develop a technique for specifying the cancer metastasis region in the inside of the sentinel lymph node with high sensitivity and high accuracy.
In Non-Patent Document 1, there is reported a state where a melanoma tumor of the auricle of a mouse is metastasized to a regional lymph node. In accordance with this, the lymph node metastasis of the cancer occurs from the vicinity of an inflow region of an afferent lymph vessel.